Second-Generation Palladium Catalyst System for Transannular C–H Functionalization of Azabicycloalkanes

This article describes the development
of a second-generation catalyst
system for the transannular C–H functionalization of alicyclic
amines. Pyridine- and quinoline-carboxylate ligands are shown to be
highly effective for increasing the reaction rate, yield, and scope
of Pd-catalyzed transannular C–H arylation reactions of azabicyclo[3.1.0]­hexane,
azabicyclo[3.1.1]­heptane, azabicyclo[3.2.1]­octane, and piperidine
derivatives. Mechanistic studies reveal that the pyridine/quinoline-carboxylates
play a role in impeding both reversible and irreversible catalyst
decomposition pathways. These ligands enable the first reported examples
of the transannular C–H arylation of the ubiquitous tropane,
7-azanorbornane, and homotropane cores. Finally, the pyridine/quinoline-carboxylates
are shown to promote both transannular C–H arylation and transannular
C–H dehydrogenation on a homotropane substrate.